Diagnosis and Treatment > Medication

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Diana Catarino Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Cristina Ribeiro Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Leonor Gomes Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Isabel Paiva Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal

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Summary

Pituitary infections, particularly with fungus, are rare disorders that usually occur in immunocompromised patients. Cushing’s syndrome predisposes patients to infectious diseases due to their immunosuppression status. We report the case of a 55-year-old woman, working as a poultry farmer, who developed intense headache, palpebral ptosis, anisocoria, prostration and psychomotor agitation 9 months after initial diabetes mellitus diagnosis. Cranioencephalic CT scan showed a pituitary lesion with bleeding, suggesting pituitary apoplexy. Patient underwent transsphenoidal surgery and the neuropathologic study indicated a corticotroph adenoma with apoplexy and fungal infection. Patient had no preoperative Cushing’s syndrome diagnosis. She was evaluated by a multidisciplinary team who decided not to administer anti-fungal treatment. The reported case shows a rare association between a corticotroph adenoma and a pituitary fungal infection. The possible contributing factors were hypercortisolism, uncontrolled diabetes and professional activity. Transsphenoidal surgery is advocated in these infections; however, anti-fungal therapy is still controversial.

Learning points:

  • Pituitary infections are rare disorders caused by bacterial, viral, fungal and parasitic infections.

  • Pituitary fungal infections usually occur in immunocompromised patients.

  • Cushing’s syndrome, as immunosuppression factor, predisposes patients to infectious diseases, including fungal infections.

  • Diagnosis of pituitary fungal infection is often achieved during histopathological investigation.

  • Treatment with systemic anti-fungal drugs is controversial.

  • Endocrine evaluation is recommended at the time of initial presentation of pituitary manifestations.

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Ana Gonçalves Ferreira Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Tiago Nunes da Silva Endocrinology Department, Portuguese Institute of Oncology Francisco Gentil, Lisbon, Portugal

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Sofia Alegria Cardiology Department, Garcia de Orta Hospital, Almada, Portugal

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Maria Carlos Cordeiro Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Jorge Portugal Endocrinology and Diabetes Department, Garcia de Orta Hospital, Almada, Portugal

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Summary

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that can secrete catecholamines. The authors describe a challenging case who presented as stress cardiomyopathy and myocardial infarction (MI). A 76-year-old man, with a medical history of Parkinson’s disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and a previous inferior MI in 2001, presented to the emergency department due to chest pain, headaches and vomiting. He also reported worsening blood glucose levels and increasing constipation over the preceding weeks. BP was 185/89 mmHg (no other relevant findings). EKG had ST segment depression in leads V2-V6, T troponin was 600 ng/L (<14) and the echocardiogram showed left ventricular hypokinesia with mildly compromised systolic function. Nevertheless, he rapidly progressed to severe biventricular dysfunction. Coronary angiogram showed a 90% anterior descendent coronary artery occlusion (already present in 2001), which was treated with angioplasty/stenting. In the following days, a very labile BP profile and unexplained sinus tachycardia episodes were observed. Because of sustained severe constipation, the patient underwent an abdominal CT that revealed a retroperitoneal, heterogeneous, hypervascular mass on the right (62 × 35 mm), most likely a paraganglioma. Urinary metanephrines were increased several fold. 68Ga-DOTANOC PET-CT scan showed increased uptake in the abdominal mass (no evidence of disease elsewhere). He was started on a calcium-channel blocker and alpha blockade and underwent surgery with no major complications. Eight months after surgery, the patient has no evidence of disease. Genetic testing was negative for known germline mutations. This was a challenging diagnosis, but it was essential for adequate cardiovascular stabilization and to reduce further morbidity.

Learning points:

  • PPGL frequently produces catecholamines and can manifest with several cardiovascular syndromes, including stress cardiomyopathy and myocardial infarction.

  • Even in the presence of coronary artery disease (CAD), PPGL should be suspected if signs or symptoms attributed to catecholamine excess are present (in this case, high blood pressure, worsening hyperglycaemia and constipation).

  • Establishing the correct diagnosis is important for adequate treatment choice.

  • Inodilators and mechanical support might be preferable options (if available) for cardiovascular stabilization prior to alpha blockade and surgery.

  • Laboratory interference should be suspected irrespective of metanephrine levels, especially in the context of treated Parkinson’s disease.

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Michelle Maher Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Mohammed Faraz Rafey Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland

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Helena Griffin Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Katie Cunningham Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland

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Francis M Finucane Bariatric Medicine Service, Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, Ireland
HRB Clinical Research Facility, National University of Ireland Galway, Galway, Ireland

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Summary

A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team.

Learning points:

  • Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss.

  • Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up.

  • For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option.

  • Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary.

  • In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.

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Senhong Lee of Endocrinology, Monash Health, Clayton, Victoria, Australia

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Aparna Morgan of Endocrinology, Monash Health, Clayton, Victoria, Australia

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Sonali Shah of Endocrinology, Monash Health, Clayton, Victoria, Australia

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Peter R Ebeling of Endocrinology, Monash Health, Clayton, Victoria, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia

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Summary

We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.

Learning points:

  • Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.

  • Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.

  • Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.

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Ken Takeshima First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Hiroyuki Ariyasu First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Tatsuya Ishibashi First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Shintaro Kawai First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Shinsuke Uraki First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Jinsoo Koh Department of Neurology, Wakayama Medical University, Wakayama,, Japan

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Hidefumi Ito Department of Neurology, Wakayama Medical University, Wakayama,, Japan

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Takashi Akamizu First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Summary

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA) axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.

Learning points:

  • DM1 patients could be affected by a variety of multiple endocrinopathies.

  • Our patients with DM1 presented rare combinations of multiple endocrinopathies; diabetes mellitus, combined form of primary and secondary hypogonadism and dysfunction of HPA axis.

  • Testosterone treatment of hypogonadism in patients with DM1 could improve body composition.

  • The patients with DM1 should be assessed endocrine functions and treated depending on the degree of each endocrine dysfunction.

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Murray B Gordon Allegheny Neuroendocrinology Center, Departments of Medicine and Neurosurgery, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA

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Kellie L Spiller Allegheny Neuroendocrinology Center, Departments of Medicine and Neurosurgery, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA

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Summary

Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin.

Learning points

  • Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide.

  • Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled.

  • Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.

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E Rapti Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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S Karras Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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M Grammatiki Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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A Mousiolis Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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X Tsekmekidou Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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E Potolidis Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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P Zebekakis Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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M Daniilidis 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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K Kotsa Diabetes Center of 1st Department of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece

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Summary

Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol.

Learning points

  • Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA).

  • Sitagliptin administration in patients with LADA might prolong the insulin-free period.

  • Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease.

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Jiman Kim
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Eulsun Moon Seoul 365 Medical Clinic, Seoul, Korea

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Seungwon Kwon Department of Cardiovascular and Neurologic Diseases, College of Korean Medicine, KyungHee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea

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Summary

Diabetic nephropathy, a microvascular complication of diabetes, is a progressive kidney disease caused by angiopathy of the capillaries in the kidney glomeruli. Herein, we report a case of a 62-year-old patient with a 30 year history of diabetes, who showed a substantial improvement in diabetic nephropathy on administration of 30 g of Astragalus membranaceus extract per day. After 1 month, estimated glomerular filtration rate increased from 47 to 72 ml/min per 1.73 m2 and was subsequently maintained at the 1-month follow-up. Urinary protein levels also decreased following treatment. Herein, we present and discuss the evidence and mechanism of A. membranaceus on diabetic nephropathy in this patient.

Learning points

  • Diabetic nephropathy is a progressive kidney disease.

  • Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are currently used to prevent and delay the progression of diabetic nephropathy. However, their effects are not sufficient to prevent a decline in kidney function.

  • Furthermore, combination therapy with an ACE inhibitor and an ARB can produce adverse effects without additional benefits.

  • In the early phase of diabetic nephropathy, administration of Astragalus membranaceus can be a therapeutic option.

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